Large Family Research Articles

Numerical analysis of a mixed-dimensional poromechanical model with frictionless contact at matrix–fracture interfaces

We present a complete numerical analysis for a general discretization of a coupled flow–mechanics model in fractured porous media, considering single-phase flows and including frictionless contact at matrix–fracture interfaces, as well as nonlinear poromechanical coupling. Fractures are described as planar surfaces, yielding the so-called mixed- or hybrid-dimensional models. Small displacements and a linear elastic behavior are considered for the matrix. The model accounts for discontinuous fluid pressures at matrix–fracture interfaces in order to cover a wide range of normal fracture conductivities. The numerical analysis is carried out in the Gradient Discretization framework (see J. Droniou, R. Eymard, T. Gallouët, C. Guichard, and R. Herbin [The gradient discretisation method, Springer, Cham, 2018]), encompassing a large family of conforming and nonconforming discretizations. The convergence result also yields, as a by-product, the existence of a weak solution to the continuous model. A numerical experiment in 2D is presented to support the obtained result, employing a Hybrid Finite Volume scheme for the flow and second-order finite elements ( P 2 \mathbb {P}_2 ) for the mechanical displacement coupled with face-wise constant ( P 0 \mathbb P_0 ) Lagrange multipliers on fractures, representing normal stresses, to discretize the contact conditions.

Status, Gaps and Perspectives of Powdery Mildew Resistance Research and Breeding in Cucurbits

Cucurbitaceae, the gourd family of flowering plants, is a very large and diverse family, the order Cucurbitales, contains 95 genera and 950–980 species of food and ornamental plants, and wild and weedy species mostly with high genetic diversity. This review is focused on the most important cucurbit crops (Cucumis sativus, Cucumis melo, Cucurbita spp., Citrullus lanatus, Momordica charantia, Lagenaria siceraria, and Luffa acutangula) and some their wild relatives as hosts of cucurbit powdery mildews (CPM). Powdery mildews (PM) (Ascomycota, Erysiphales) are one of the most frequently encountered and easily visible groups of plant pathogenic fungi with > 900 species. They are obligate biotrophs, they colonize above-ground plant tissues, mostly leaves, though they may also colonize stems, petioles, flowers and fruits, and they are usually debilitators, not killers. These parasitic fungi have been problematic on cucurbits for a long time world-wide, causing serious economic losses in yield and quality. All economically important cucurbit crops host CPM. Seven PM species with different taxonomic positions, host ranges, geographic distributions and ecological requirements are known on cucurbits. CPM species taxonomy and denomination rapidly changed during last few decades through detailed analyses and clarifications. At least three PM species frequently parasitize cucurbits: the endoparasite Leveillula taurica (Lt) with marginal economic importance; and two ectoparasitic species, Golovinomyces orontii (Go), and Podosphaera xanthii (Px), which are economically important world-wide. The two pathogens differ in ecological requirements and distribution, though they may occur together in mixed infections. They are highly variable at the population level for virulence, race identities, and fast adaptation of pathogens. Cucurbit-CPM species interactions are diverse and complicated, and differ between hosts and their respective pathogen genera and species. Here we present a critical overview of obstacles, gaps and recent progress in these matters for six cucurbit genera with respect to resistance resources, genetics of resistance, genetic mapping and development of molecular markers, physiology and mechanisms of resistance, developments in mlo-mediated resistance, patents, and CPM resistance breeding.

GhCTSF1, a short PPR protein with a conserved role in chloroplast development and photosynthesis, participates in intron splicing of rpoC1 and ycf3-2 transcripts in cotton

Cotton is one of the most important textile fibers worldwide. As crucial agronomic traits, leaves play an essential role in the growth, disease resistance, fiber quality, and yield of cotton plants. Pentatricopeptide repeat (PPR) proteins are a large family of nuclear-encoded proteins involved in organellar or nuclear RNA metabolism. Using a virus-induced gene silencing assay, we found that cotton plants displayed variegated yellow leaf phenotypes with decreased chlorophyll content when expression of the PPR gene GhCTSF1 was silenced. GhCTSF1 encodes a chloroplast-localized protein that contains only two PPR motifs. Disruption of GhCTSF1 substantially reduces the splicing efficiency of rpoC1 intron 1 and ycf3 intron 2. Loss of function of the GhCTSF1 ortholog EMB1417 causes splicing defects in rpoC1 and ycf3-2, leading to impaired chloroplast structure and decreased photosynthetic rates in Arabidopsis. We also found that GhCTSF1 interacts with two splicing factors, GhCRS2 and GhWTF1. Defects in GhCRS2 and GhWTF1 severely affect intron splicing of rpoC1 and ycf3-2 in cotton, leading to defects in chloroplast development and a reduction in photosynthesis. Our results suggest that GhCTSF1 is specifically required for splicing rpoC1 and ycf3-2 in cooperation with GhCRS2 and GhWTF1.

Functional Study of SNCA p.V15A Variant: Further Linking α-Synuclein and Glucocerebrosidase.

SNCA p.V15A was reported in five families. In vitro models showed increased aggregation and seeding activity, mitochondrial damage, and apoptosis. Mutant flies had reduced flying ability and survival. To clinically and functionally evaluate SNCA p.V15A in a large Italian family with Parkinson's disease (PD). Genetic diagnosis was reached through next-generation sequencing. Pathogenicity was assessed by molecular dynamics simulation and biochemical studies on peripheral blood mononuclear cells (PBMCs). Five siblings carried SNCA p.V15A; three developed bradykinetic-rigid PD in their 50s with rapid motor progression and variable cognitive impairment. A fourth sibling had isolated mood disturbance, whereas the fifth was still unaffected at age 47. The mutant protein showed decreased stability and an unstable folded structure. Proband's PBMCs showed elevated total and phosphorylated α-synuclein (α-syn) levels and significantly reduced glucocerebrosidase activity. This study demonstrates accumulation of α-synV15A in PBMCs and strengthens the link between α-syn pathophysiology and glucocerebrosidase dysfunction. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Speaker Attribution in German Parliamentary Debates with QLoRA-adapted Large Language Models

The growing body of political texts opens up new opportunities for rich insights into political dynamics and ideologies but also increases the workload for manual analysis. Automated speaker attribution, which detects who said what to whom in a speech event and is closely related to semantic role labeling, is an important processing step for computational text analysis. We study the potential of the large language model family Llama 2 to automate speaker attribution in German parliamentary debates from 2017-2021. We fine-tune Llama 2 with QLoRA, an efficient training strategy, and observe our approach to achieve competitive performance in the GermEval 2023 Shared Task On Speaker Attribution in German News Articles and Parliamentary Debates. Our results shed light on the capabilities of large language models in automating speaker attribution, revealing a promising avenue for computational analysis of political discourse and the development of semantic role labeling systems.

Applying the modified UV-activated TOP assay to complex matrices impacted by aqueous film-forming foams

Per- and polyfluoroalkyl substances (PFAS) are a large chemical family, and numerous chemical species can co-exist in environmental samples, especially those impacted by aqueous film-forming foams (AFFFs). Given the limited availability of chemical standards, capturing the total amount of PFAS is challenging. Thus, the total oxidizable precursor (TOP) assay has been developed to estimate the total amount of PFAS via the oxidative conversion of precursors into perfluorocarboxylic acids (PFCAs). This study aims to enhance the robustness of the TOP assay by replacing heat activation with UV activation. We evaluated the molar yields of known precursors in water in the presence of varying levels of Suwannee River natural organic matter (SRNOM) and in two soils. The impact of UV activation was also evaluated in two soils spiked with three well-characterized AFFFs, six AFFF-impacted field soils, and nine rinse samples of AFFF-impacted stainless-steel pipe. In the presence of 100 mg/L SNROM, 6:2 fluorotelomer sulfonate (FTS), 8:2 FTS, and N-ethyl perfluorooctane sulfonamidoacetic acid (N-EtFOSAA) in deionized water had good molar recovery as PFCAs (average of 102 ± 9.8 %); at 500 mg/L SNROM, the recovery significantly dropped to an average of 51 ± 19 %. In two soils (with 4 % and 8.8 % organic matter) with individual precursor spikes, the average molar recovery was 101 ± 9.4 %, except N-EtFOSAA, which had a reduced recovery in the soil with 8.8 % organic matter (OM). UV-activated assays outperformed heat-activated ones, especially in AFFF-impacted soils and pipe extract samples, with an average of 1.4–1.5× higher PFCA recovery. In almost all test samples, UV activation resulted in a notable shift towards longer PFCA chain lengths, particularly for samples with high OM content. The study confirmed the advantages of UV activation, including a significantly shortened exposure time (1 h vs. 6 h) and reduced matrix effects from OM due to the dual functions of UV in activating persulfate and photodegrading OM.

Recent Progress in Covalent Organic Frameworks for Cathode Materials.

Covalent organic frameworks (COFs) are constructed from small organic molecules through reversible covalent bonds, and are therefore considered a special type of polymer. Small organic molecules are divided into nodes and connectors based on their roles in the COF's structure. The connector generally forms reversible covalent bonds with the node through two reactive end groups. The adjustment of the length of the connector facilitates the adjustment of pore size. Due to the diversity of organic small molecules and reversible covalent bonds, COFs have formed a large family since their synthesis in 2005. Among them, a type of COF containing redox active groups such as -C=O-, -C=N-, and -N=N- has received widespread attention in the field of energy storage. The ordered crystal structure of COFs ensures the ordered arrangement and consistent size of pores, which is conducive to the formation of unobstructed ion channels, giving these COFs a high-rate performance and a long cycle life. The voltage and specific capacity jointly determine the energy density of cathode materials. For the COFs' cathode materials, the voltage plateau of their active sites' VS metallic lithium is mostly between 2 and 3 V, which has great room for improvement. However, there is currently no feasible strategy for this. Therefore, previous studies mainly improved the theoretical specific capacity of the COFs' cathode materials by increasing the number of active sites. We have summarized the progress in the research on these types of COFs in recent years and found that the redox active functional groups of these COFs can be divided into six subcategories. According to the different active functional groups, these COFs are also divided into six subcategories. Here, we summarize the structure, synthesis unit, specific surface area, specific capacity, and voltage range of these cathode COFs.

Molecular survey and genetic diversity of Plasmodium sp. infesting domestic poultry in northeastern Thailand.

Haemosporidian parasites are prevalent worldwide and can cause economic losses in poultry production. These parasites are arousing interest in Thailand and are found in many avian species. There is insufficient information on the genetic diversity of these alveolates from the largest families - Plasmodidae, Haemoprotidae and Leucocytozoidae - specifically parasitising ducks, turkeys, and geese. Blood samples from 116 backyard poultry (60 ducks, 36 turkeys and 20 geese) in northeastern Thailand were investigated for Plasmodium spp., Haemoproteus spp. and Leucocytozoon spp. infections using microscopic examination and molecular approaches. A total of 37/116 birds (31.9%) had confirmed Plasmodium infections. The prevalence was 69.4% (25/36) in turkeys, 18.3% (11/60) in ducks, and 5.0% (1/20) in geese. Of these 37 positives, 86.5% were Plasmodium sp., 10.8% were P. gallinaceum and 2.7% were P. juxtanucleare. Sequence analysis based on the cytochrome b gene identified seven lineages, of which two were new lineages in backyard poultry. This is the first report on the prevalence of haemosporidian parasites in backyard poultry in northeastern Thailand. The results provide important data for better understanding the molecular epidemiology of haemosporidian parasites infection in poultry in this region, which will be helpful in controlling these blood parasites.

Landwirtschaft im nationalen Wettbewerb und die Rolle des Bodenmarktes

Abstract German agriculture exhibits persistent income problems. While larger farms are on average quite profitable, this is consistently not true for the majority of part-time and small- and medium-sized family farms. These farms are particularly prominent in the southern and western parts of Germany while larger family and corporate farms dominate the north and the east. Competition among farms is fierce on land markets. Particularly regions with smaller farms exhibit high land prices, often higher than the Ricardian land rents. This market disequilibria as well as the persistence of income deficits for small farms can be attributed to agricultural subsidies, tax benefits and legal privileges.

Coexistent HCN4 and GATA5 Rare Variants and Atrial Fibrillation in a Large Spanish Family

BackgroundFamilial association of atrial fibrillation (AF) can involve single gene variants related to known arrhythmogenic mechanisms; however, genome-wide association studies often disclose complex genetic variants in familial and nonfamilial AF, making it difficult to relate to known pathogenetic mechanisms. MethodsThe finding of 4 siblings with AF led to studying 47 members of a family. Long-term Holter monitoring (average 298 hours) ruled out silent AF. Whole-exome sequencing was performed, and variants shared by the index cases were filtered and prioritised according to current recommendations. HCN4 currents (IHCN4) were recorded in Chinese hamster ovary cells expressing human p.P1163H or native HCN4 channels with the use of the patch-clamp technique, and topologically associated domain analyses of GATA5 variant carriers were performed. ResultsThe clinical study diagnosed 2 more AF cases. Five family members carried the heterozygous p.P1163H HCN4 variant, 14 carried the intronic 20,61040536,G,A GATA5 rare variant, and 9 carried both variants (HCN4+GATA5). Five of the 6 AF cases (onset age ranging from 33 to 70 years) carried both variants and 1 carried the GATA5 variant alone. Multivariate analysis showed that the presence of HCN4+GATA5 variants significantly increased AF risk (odds ratio 32.740, 95% confidence interval 1.812-591.408) independently from age, hypertension, and overweight. Functional testing showed that IHCN4 generated by heterozygous p.P1163H were normal. Topologically associating domain analysis suggested that GATA5 could affect the expression of many genes, including those encoding microRNA-1. ConclusionThe coincidence of 2 rare gene variants was independently associated with AF, but functional studies do not allow the postulation of the arrhythmogenic mechanisms involved.

Истории связующие нити. Ярославль и Сергей Иванович Спасокукоцкий

Biography of Sergey Spasokukotsky, the outstanding Russian surgeon, is closely related to the Yaroslavl Territory. He spent his childhood in the Danilovsky region, coming from a large and friendly family of a zemstvo doctor. In 1880–1888, he studied at the Men’s Gymnasium after his family had moved to Yaroslavl. The building now belongs to the Yaroslavl State Medical University where a representative of his scientific school, Professor Busalov AA, worked decades later. Life and activity of Sergey Spasokukotsky represent a bright example of unselfish service to medicine. Being a graduate of the Emperor’s Moscow University, he had a chance to continue his medical career in Moscow but went to the province where he worked as a zemstvo doctor for many years, actively implementing advance achievements of medicine into abdominal surgery, neurosurgery, pulmonary surgery, creating novel and modifying available surgeries. S. Spasokukotsky and his student developed an affordable and effective method of preparing a surgeon’s hands for a surgery with 0.5% ammonia solution (method by Spasokukotsky and Kochergyn). The scientific and practical activities of Sergey Spasokukotsky resulted in the development of a large scientific school with an ultimate scientific social responsibility, originality, great depth and boldness while solving the issues of surgical pathology.

Super band gaps and periodic approximants of generalised Fibonacci tilings

We present mathematical theory for self-similarity induced spectral gaps in the spectra of systems generated by generalised Fibonacci tilings. Our results characterise super band gaps, which are spectral gaps that exist for all sufficiently large periodic systems in a Fibonacci-generated sequence. We characterise super band gaps in terms of a growth condition on the traces of the associated transfer matrices. Our theory includes a large family of generalised Fibonacci tilings, including both precious mean and metal mean patterns. We apply our analytic results to characterise spectra in three different settings: compressional waves in a discrete mass-spring system, axial waves in structured rods and flexural waves in multi-supported beams. The theory is shown to give accurate predictions of the super band gaps, with minimal computational cost and significantly greater precision than previous estimates. It also provides a mathematical foundation for using periodic approximants (supercells) to predict the transmission gaps of quasicrystalline samples, as we verify numerically.

Environmental exposure to glyphosate does not inhibit human acetylcholinesterase and butyrylcholinesterase.

Glyphosate has remained the leading herbicide on the global market to date, despite the continuous debate between consumers, scientific community, and regulatory agencies over its carcinogenicity, genotoxicity, environmental persistence, and the role in the development of neurodegenerative disorders. Chemically, glyphosate belongs to a large family of organophosphorus pesticides, which exert a neurotoxic effect by inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), enzymes of the cholinergic system essential for maintaining neurotransmission. Although research shows that glyphosate is a weak cholinesterase inhibitor in fish and mammals compared to other OP compounds, no conclusive data exist concerning the inhibition of human AChE and BChE. In our study we analysed its inhibitory potency on human AChE and BChE, by establishing its IC50 and reversible inhibition in terms of dissociation inhibition constants. Glyphosate concentration of 40 mmol/L caused near total inhibition of enzyme activity (approx. 10 % activity remaining). Inhibition dissociation constants (K i) of glyphosate-AChE and -BChE complexes were 28.4±2.7 mmol/L and 19.3±1.8 mmol/L, respectively. In conclusion, glyphosate shows a slight binding preference for BChE but exhibits inhibition only in a high concentration range. Our results are in line with studies reporting that its neurotoxic effect is not primarily linked to the cholinergic system.

Is it time to end the use of base deficit for fetal well-being assessment?

Authors have expressed reservations regarding the use of base deficit measured in umbilical artery blood samples to assess fetal well-being during the course of labor and to predict neonatal neurologic morbidity. Despite its integration into clinical practice for more than 50 years, obstetricians and maternal-fetal medicine specialists may not realize that this marker has significant limitations in accurately identifying neonatal metabolic acidosis as a proxy for fetal well-being. In brief, there are 2 large families of base deficit, namely whole blood and extracellular fluid. Both rely on equations that use normal adult acid-base characteristics (pH 7.40 and partial CO2 pressure of 40 mm Hg) that overlook the specificity of the normal in utero acid-base status of pH 7.27 and partial CO2 pressure of 54 mm Hg. In addition, it ignores the unique characteristic of the in utero fetal response to acute hypoxia. The dependence on placental circulation for CO2 elimination may lead to extremely high values (up to 130 to 150 mm Hg) during hypoxic events, a phenomenon that is absent in adults with acute metabolic acidosis who can hyperventilate. The dispute over if to include a correction for high partial CO2 pressure in the bicarbonate estimation, as presented in the Great Trans-Atlantic Debates, remains unresolved. The key constants computed for adult acid-base physiology in the current base deficit algorithms, without accounting for the impact of high partial CO2 pressure or other fetal characteristics of buffering capacity (eg, differences in body water content composition, plasma protein, and hemoglobin attributes), may lead to an overestimation of metabolic acidosis, especially in newborns who are experiencing hypercarbia during the early stages of the hypoxic response. These unrecognized limitations impact the base deficit results and may mislead clinicians on fetal well-being assessments when discussing the management of fetal heart rate monitoring and neonatal outcomes. Based on our arguments, we believe that it is prudent to consider an alternative to base deficit for drawing conclusions regarding fetal well-being during the course of birth management. We propose a marker specifically related to the newborn acid-base physiology--the neonatal eucapnic pH correction. This marker can be added to arterial cord blood gas analysis, and we have described how to interpret it as a marker of neonatal metabolic acidosis.

Examining toilet use and menstrual hygiene practices among beneficiary households of Swachh Bharat Abhiyaan (Clean India Mission) in rural areas of Mayurbhanj district of Odisha, India.

Basic sanitation and waste management have always remained a central issue in India. The country launched its flagship sanitation program - Swachh Bharat Abhiyan (SBA) (Clean India Mission) in 2014 to abolish open defecation and achieve universal sanitation coverage. This study aimed to examine barriers to toilet use and women's menstrual hygiene practices in relation to the availability of toilets among rural residents. Using a cross-sectional design and multi-stage sampling method, 120 households were selected from rural villages of the Mayurbhanj district of Odisha. Structured questionnaires and direct observation methods were used for data collection. All the houses had SBA latrines, yet 25% population defecated outside. About 40% households reportedly never cleaned their toilets. Most menstruating women (86.2%) preferred to change their menstrual pads/cloths in their bedroom instead of bathrooms. Incomplete construction was reported as the major reason for not using toilets. Large family size and low caste were found to be other predictors of non-use of toilets. Rural women did not use toilets for menstrual purposes as they do not consider these places as clean and safe. This study clearly suggests that constructing toilets without adequate behaviour change interventions would not solve the problem of hygiene and sanitation in India, particularly in rural areas. There must be adequate monitoring of SBA scheme and utilization of funds for toilet usage. Development and implementation of suitable behaviour change strategies for toilet use in rural areas are essential to achieve the goal of open defaecation-free India.

Corona virus – A natural catastrophe

Viruses, ultra-microscopic structures mainly are pathogens, which affect the human beings by causing endemic, epidemic and even pandemic diseases. Coronaviruses (CoV) - large family of enveloped viruses containing single stranded RNA, belong to the family: Coronaviridae, order: Nidovirales. Zoonotic coronaviruses have emerged in recent years to cause human outbreaks such as SARS - severe acute respiratory syndrome, MERS - Middle East respiratory syndrome and coronavirus disease 2019 (COVID-19). SARS-like CoVs observed in horse shoe bats like Rhinolophus macrotis & R.sinicus which shed the virus in saliva and urine transmitting to human beings during the processing of bat meat. SARS-CoV-2 virions attach to human cells manifested as a respiratory infection. The clinical spectrum of illness varies from no symptoms or mild respiratory symptoms to severe, rapidly progressive pneumonia, acute respiratory distress syndrome, septic shock, or multi organ failure resulting in death. There are many ways of diagnosis of COVID-19 through thermal checking for fever, symptoms like severe cough, cold etc., lung X-ray, antibody detection and PCR tests. ‘Prevention is better than cure’, a common proverb has lot of meaning in the present pandemic. Physical distancing, wearing mask in public places, sanitizing hands are now considered as most important steps in preventing COVID-19. Recently designated Omicron subvariant JN.1 is spreading causing the disease among the people. Probiotic drinks play an important role in inhibiting the ACE inhibiting biopeptide, preventing virus fusion to human lung cells and studies are going on in this aspect. Globally many vaccines have been released and used providing the immunity against the COVID-19. The present review article focuses on virus, classification, place of coronavirus, its impact on humans, clinical manifestation, prevention and control measures.

Using Total Cohort Fertility in Adolescence (TCFA) to analyse adolescent fertility trends and factors in Niger: Evidence from 1992 to 2012 demographic and health surveys.

Girls aged 10-19 currently represent 12% of Niger's population (2020). And this number continues to grow as the fertility rate is higher while mortality is declining faster. Using Niger's demographic and health surveys carried out between 1992 and 2012, the study investigated adolescent fertility, its trends and associated factors. It mobilised descriptive methods (Total cohort fertility in adolescence (TCFA) computation, distribution of the number of adolescent births, and computation of adolescent cohort childbearing mean age) and multivariate Logistic and Poisson models. The result shows the TCFA went from 1.29 in 1992 to 1.17 in 2012. Early sexual intercourse and marriage, infant mortality, the desire for a large family, and urbanisation are among the factors significantly associated with adolescent fertility in Niger. The study concludes that the high level of adolescent fertility in Niger does not seem to be changing.

Opinions, attitudes and perceptions of local people towards the conservation of Nigeria‐Cameroon chimpanzees in Mpem‐Djim National Park, central Cameroon

Abstract Local ecological knowledge (LEK), tied to specific cultures, is crucial for sustainability in conservation initiatives. Therefore, including holders of this knowledge in management decisions is essential. Collecting protected area‐specific data on local people's attitudes, opinions and perceptions towards wildlife, especially for highly threatened species like great apes, is therefore crucial for effective conservation. This study emphasizes the importance of LEK as an interdisciplinary approach, highlighting its essential role in informing conservation decisions and understanding human–environment interactions. To fill the information gap on the LEK on the Nigeria‐Cameroon chimpanzee in central Cameroon, we used questionnaires to assess the LEK of respondents specifically their perceptions, opinions and attitudes towards the population trend of chimpanzees, as well as their opinion about the current management systems of Mpem and Djim National Park. We collect data from 240 respondents in 15 villages in the neighbourhood of the park. Using generalized linear mixed models, we were also able to assess socioeconomic and demographic factors that correlate with the opinions, attitudes and perceptions of the respondents towards chimpanzee conservation. About 87% of the respondents exhibited good knowledge about chimpanzees and 59% reported taboos related to chimpanzees. About 94% were aware of laws that prohibit the hunting of chimpanzees, while 87% agreed that it is a good initiative to conserve chimpanzees, and 42% reported that their population increased. Almost half (52%) of the respondents said they were satisfied with the current park management system. Age, gender, education level, number of children in the household and time spent in the community were predictors that influenced the attitude, opinion and perception of the respondents while occupation and the geographic distance between the village and the park did not. Our findings suggest that raising awareness of human–chimpanzee coexistence through adult education programmes should target specific demographic groups, such as those with larger families, limited education, older age, individuals with lower LEK or native. These findings brought insights to guide future studies and should be taken into account when discussing regional management. Read the free Plain Language Summary for this article on the Journal blog.

Use of 3-Deoxy-D-arabino-heptulosonic acid 7-phosphate Synthase (DAHP Synthase) to Enhance the Heterologous Biosynthesis of Diosmetin and Chrysoeriol in an Engineered Strain of Streptomyces albidoflavus.

Flavonoids are a large family of polyphenolic compounds with important agro-industrial, nutraceutical, and pharmaceutical applications. Among the structural diversity found in the flavonoid family, methylated flavonoids show interesting characteristics such as greater stability and improved oral bioavailability. This work is focused on the reconstruction of the entire biosynthetic pathway of the methylated flavones diosmetin and chrysoeriol in Streptomyces albidoflavus. A total of eight different genes (TAL, 4CL, CHS, CHI, FNS1, F3'H/CPR, 3'-OMT, 4'-OMT) are necessary for the heterologous biosynthesis of these two flavonoids, and all of them have been integrated along the chromosome of the bacterial host. The biosynthesis of diosmetin and chrysoeriol has been achieved, reaching titers of 2.44 mg/L and 2.34 mg/L, respectively. Furthermore, an additional compound, putatively identified as luteolin 3',4'-dimethyl ether, was produced in both diosmetin and chrysoeriol-producing strains. With the purpose of increasing flavonoid titers, a 3-Deoxy-D-arabino-heptulosonic acid 7-phosphate synthase (DAHP synthase) from an antibiotic biosynthetic gene cluster (BGC) from Amycolatopsis balhimycina was heterologously expressed in S. albidoflavus, enhancing diosmetin and chrysoeriol production titers of 4.03 mg/L and 3.13 mg/L, which is an increase of 65% and 34%, respectively. To the best of our knowledge, this is the first report on the de novo biosynthesis of diosmetin and chrysoeriol in a heterologous host.

Discovering New Substrates of a UDP-Glycosyltransferase with a High-Throughput Method.

UDP-glycosyltransferases (UGTs) form a large enzyme family that is found in a wide range of organisms. These enzymes are known for accepting a wide variety of substrates, and they derivatize xenobiotics and metabolites for detoxification. However, most UGT homologs have not been well characterized, and their potential for biomedical and environmental applications is underexplored. In this work, we have used a fluorescent assay for screening substrates of a plant UGT homolog by monitoring the formation of UDP. We optimized the assay such that it could be used for high-throughput screening of substrates of the Medicago truncatula UGT enzyme, UGT71G1, and our results show that 34 of the 159 screened compound samples are potential substrates. With an LC-MS/MS method, we confirmed that three of these candidates indeed were glycosylated by UGT71G1, which includes bisphenol A (BPA) and 7-Ethyl-10-hydroxycamptothecin (SN-38); derivatization of these toxic compounds can lead to new environmental and medical applications. This work suggests that UGT homologs may recognize a substrate profile that is much broader than previously anticipated. Additionally, it demonstrates that this screening method provides a new means to study UDP-glycosyltransferases, facilitating the use of these enzymes to tackle a wide range of problems.